Your Digest for Monday, Oct 02, 2023 10:59 PM


#2022GM/Q09
#2022BSQ-NOV/Q18
#2020BSQ-NOV/Q56

"Paraneoplastic syndromes refer to groupings of symptoms that occur in patients with malignant neoplasms that cannot be readily explained by local invasion or distant metastasis of the tumor, or the elaboration of hormones indigenous to the tissue of origin of the neoplasm. Paraneoplastic syndromes occur in 10–15% of cancer patients."
Definition of paraneoplastic syndromes in Robbin's Basic Pathology:
They can be triggered by an abnormal immune response to the tumour, or by substances secreted by the neoplasm itself.

  1. Cushing's syndrome due to ectopic ACTH production
  2. non bacterial thrombotic endocarditis caused by hypercoagulability.
    1. The term nonbacterial thrombotic endocarditis (NBTE), or marantic endocarditis, refers to a spectrum of lesions ranging from microscopic aggregates of platelets to large vegetations on previously undamaged heart valves (most often aortic and mitral) in the absence of a bloodstream bacterial infection. Source
      The cancers most commonly associated with paraneoplastic syndromes (PNS) are

Hypercoagulability
Trousseau syndrome - migratory thrombophlebitis occuring in association with malignancy.
Nephrotic syndrome - commonest cause is membranous nephropathy.
HPO - hypertrophic pulmonary osteoarthropathy (clubbing of fingers and toes)
Inflammatory myopathies - [[2021 General Medicine July#Polymyositis and dermatomyositis|DM and PM]]

Carcinoid tumours :

The most common biologically active substance secreted from carcinoid tumors is 5-HT (serotonin), a vasoactive peptide whose biosynthesis is accomplished nearly exclusively by the enterochromaffin cells. Synthesized from the amino acid tryptophan, the release of 5-HT into the systemic circulation can cause the classic symptoms of the carcinoid syndrome, which include diarrhea, episodic flushing, bronchoconstriction, and eventual right-sided valvular heart disease


granulomaAnulare.pngImageSource


[[Hypertension in pregnancy#Paraneoplastic syndromes associated with lung cancer]]



erythropoietinProducingCellsPeritubular.png


Eosinophilic oesophagitis

Incidence is increasing.
Symptoms:

Barrett oesophagus

#2020BSQ-NOV/Q51

Pathology of myocardial infarction

Gross Morphologic features of the heart following MI

[!INFO] Changes after MI: A summary of the changes given in Robbins.

mnemonicMyocardialChangesFollowingMI.png
myocardialInfarctionPathologyChangesTimeCourse.png

Myocardial rupture

Fibrosarcoma

#2020BSQ-NOV/Q56

Renal tumours

Benign tumours are of no clinical significance as benign cortical papillary adenomas occur in about 40% of adults.

Renal cancers are mainly of 3 types

Symptoms:

Neck examination

neckExamination.jpeg


Symptoms are may be flu like; about 15% develop lymphadenopathy (painless) (usually head and neck) . Symptoms resolve spontaneously in a few weeks to months;

Pyrimethamine is an antiparasitic prescription medicine

Congenital toxoplasmosis;


- Live cysts: Antihelminthing treatment must be combined with steroid which penetrates the BBB (Dexamethasone) to lessen the inflammatory response elicited following death of the parasite. 

Granuloma formation and patterns

A good detailed Source

[!INFO] Exerpt from the summary of the article above:

Granuloma formation is a histologic pattern of chronic inflammation.
The pattern of inflammation can be classified in many ways. (necrotizin or not / Suppurative or not etc.)
This corresponds to the features of the granuloma after 'maturation'.
The prototypes are

effectsOfTCellsInGranulomas.png

| Crohn's disease | Occasional non caseating granulomas with dense fibrous infiltrate |

Their membranes begin to interdigitate and the nuclei swell.

Granulomatous diseases

  1. Naked granulomas - only sparse lymphocytic infiltrate at margin of granuloma; is a typical sarcoid lesions.

  2. Suppurative granulomas - have neutrophils at the center.

    1. Fungal causes
    2. Bacterial causes
    3. Atypical mycobacteria
    4. Pyoderma gangrenosum
    5. Parasitic : leishmaniasis
  3. Tuberculoid granuloma - caseous necrosis

    1. Usually in TB. Not in leprosy.
  4. Foreign body granulomas

    1. Berylliosis
    2. Silicosis
  5. Necrbiotic - contains altered collagen in the center. Also has acellular substances in the center.

    1. Divided into red and blue granulomas depending on the stain colour.
      1. Eosinophils are red.

Ascariasis

ascarisLumbricoidesAdultAndEggs.png
ascarisLumbricoides.png

Treatment:




Lung fibrosis

Drugs causing lung fibrosis

  1. Nitrofurantoin
  2. Methotrexate
  3. Amiodarone
  4. Cancer chemotherapy
  5. Biologic agents
  6. Radiation - Acute pneumonitis - 4 to 12 weeks after therapy, Late - 6 to 12 months after.

[!INFO]
Is pulmonary fibrosis due to drugs dose or time dependant?

Vasculitides / Vasculitis

vasculitides.png
Classification of vasculitides
Good article on pulmonary vaculitis

#2021SBR-JULQ16

Main groups of vasculitis

  1. Primary
    1. Primary idiopathic
      1. Small vessel - ANCA Associated vasculitides - GPA / Wegener's, MPA, EGPA /Churgg Strauss
      2. Medium vessel - PAN, Kawasaki
      3. Large vessel - Giant cell, Takayasu
    2. Primary immune complex mediated - eg. Goodpasture's syndrome (Goodpasture's has less recurrence than GPA - PasTest answers); From the image above, these are small vessel vasculitidies.
      1. Goodpastures's
      2. Henoch-Schonlein purpura
      3. Behcet' disease
      4. IgA nephropathy.
  2. Secondary
    1. Secondary to other autoimmune diseases

Large vessel vasculitides

largeVesselVasculitidesTypes.png

Polymyalgia rheumatica

polymyalgiaLimbGirdlePattern.png
Patient it always > 50 years old; sudden onset pain and stiffness (but not weakness) of limb girdles / proximal muscles, associated with raised inflammatory markers.
ALP and gamma GT may be elevated.
Giant cell arteritis is seen in 30% of cases.
Treatment: 15mg prednisilone mane : improvement is significant in 24 to 48 hours.

Giant cell arteritis

#2022SBR Q8
#2021GM-JUL/Q17

[!INFO] The most common idiopathic systemic vasculitis.
Females >>> males (3:1)
Always over 50;
Commonest in scandinavians.
giantCellArteritisMnemonic.png

Takayasu arteritis

Affects the largest vessels in the body: the aorta and it's branches.
Mostly affects women of childbearing age!
AKA pulseless disease or aortic arch syndrome.

[!INFO]
Complete obstruction of the left common carotid
takayasu.jpg

(eg, bruit, especially carotid; blood pressure difference of extremities, difference in pulse volume, claudication, hypertension)
Steroids are the mainstay.
Diagnosis: MR angiograms.
Post prandial abdominal pain, diarrhoea, GI haemorrhage.

Medium vessel vasculitides

Polyarteritis nodosa (PAN)

The immune complex mediated medium vessel vasculitis.

[!INFO] Pathology
Segmental, transmural, necrotizing inflammation.
Characteristically, all stages of inflammation are present in different vessels / same vessel.

polyarteritisNodosaVasculitis.png

robbinWilliamsPAN.jpeg
Robbin williams : As a middle aged man, playing Peter PAN!

1/3 of patients have chronic hepatitis B infection.
Occurs in middle aged men; associated with severe systemic symptoms.
Fibrinoid necrosis of vessel walls -> thrombosis and infarction.
Probably immune complex mediated (as it's sometimes associated Hep B).
Involves ==small arteries within the organs==.
Frequency of involvement : Kidney > heart > liver > GI tract
4. Renal: haematuria and proteinuria.
5. Coronary arteritis causing MI.
6. Liver
7. Bowel ischemia -> acute abdominal pain, necrosis and bleeding
9. Mononeuritis mulitiplex - vaso vasorum infarctions
10. Skin - subcutaneous haemorrhage and gangrene
11. Somehow, lungs aren't involved.

Treatment: Corticosteroids +/- azathioprine.

Kawasaki disease

Predominantly occurs in children < 5 years old.
Systemic medium vessel arteritis. The main problems are due to coronary ischemia caused by coronary artery vasculitis leading to

  1. coronary aneurysms
  2. thrombosis.

Pathology: transumural inflammation seen but not as severe as PAN.

Treatment:
Steroids to now show benefit!
Single dose of Iv-Ig followed by aspirin.

Small vessel vasculitides

[!TIP] Mnemonic
ANCAPositiveVasculitidesMnemonic.png

Small vessel vasculitedes are divided into

  1. ANCA-associated vasculitis (AAV) - paucity of vessel wall immunoglobulin and presence of ANCA.
    3. MPA (Microscopic polyangitis) - no other name.

    1. GPA (Granulomatosis with polyangitis) - Wegener's ganulomatosis
    2. EGPA (Eosinophilic granulomatosis with polyangiitis)- Churg Strauss syndrome
  2. Immune complex SVV - prominence of vessel wall immunoglobulin.

[!INFO] Features common to small vessels vasculitides
Of vasculitidies, small vessel vasculitides commonly affect the lungs.
Small vessel vasculitides are ANCA positive.
Frequent kidney involvement

epidemiologySmallVesselVasculitis.png
mnemonic: G for greenwich ; GPA is in europe.

GPA and MPA

[!INFO] Types of ANCA antibodies
It was found that the serum of patients with vasculitis would stain neutrophils in one of two pattersn:

  1. Perinuclear - this serum has p-ANCA antibodies
  2. Cytoplasmic - this serum has c-ANCA antibodies.
    C-ANCA stains neutrophil proteinsase 3 (PR3 ANCA = cANCA)
    P-ANCA stains neurtrophil myeloperoxidase (MPO ANCA = pANCA)
    C3POcANCA-PR3ANCA.png
    c in C3PO and 3 is also in C3PO

pANCA - MPA and EGPA
cANCA - GPA
" c " in c-ANCA looks like " G " in GPA.

should be suspected in any patient who presents with
constitutional symptoms along with
clinical evidence of glomerulonephritis,
upper or lower respiratory tract involvement, or multiple mononeuropathy.

Fortunately for US, MPA and GPA are similar diseases but with some differences.
They present in older adults.

most commonly affected organs are upper and lower respiratory tract and kidneys.

URT - Otitis (even hearing loss), bloody nasal discharge, crusting, oral or nasal ulcers.
LRT - hoarseness, dry cough, pleuritic chest pain, life threatening haemoptysis.
Kidney - rapidly proliferative glomerulonephritis. -> nephritic picture
Skin - purpura of lower extremeties.

GPA and MPA are similar but differ in the following:

GPA MPA
Granuloma + ("granulomatosis") Granuloma (-)
Relapse risk is much higher Lower relapse risk
Acute kidney involvement (necrosis and crescents) Chronic lesions (tubulointerstitial fibrosis / glomerulosclerosis
PR3-ANCA type MPO-ANCA
GPA - europe MPA - East asia

GPA

[!TIP] Otitis, sinusitis, cough and glomerulonephritis and an older adult

GPA is the commonest ANCA associated vasculitis.
It is a granulomatous disease. The granulomas are not well formed like those in TB or sarcoidosis.
However, the granulomas can obstruct blood vessels and are necrotizing granulomas.

Lungs: Liquefactive necrosis seen in granulomas.
Kidneys: Focal necrotizing glomerulonephritis with crescents and thrombosis.

Affects older adults.
c-ANCA positive.

Upper respiratory tract : sinusitis , ears -> Otitis media.
Glomerulonephritis is present.

Diffuse alveolar haemorrhage and life threatening haemoptysis occurs in upto 45%.
Cough, dysponoea, pleuritic chest pain.

Staining pattern characteristic of each ANCA type
c-ANCA - diffuse staining
p-ANCA - perinuclear staining

EGPA

Presents in early adulthood.
Eosinophilia+
Allergic rhinitis and asthma that's difficult to control.
p-ANCA positive. (=MPO ANCA)

Systemic vasculitis develops later:

  1. Tender subcutaneous nodules
  2. Mononeuritis multiplex
  3. heart
  4. Kidneys

Responds well to steroids.